Magnetic nanoparticles are increasingly applied for diagnostic and therapeutic purposes. They show a set of interesting physical properties including controllable sizes ranging from ten to several hundred nanometers, a high saturation magnetization and superparamagnetic behaviour. Their small size enables them to penetrate the endothelial walls that form the interface between circulating blood or lymph and the rest of the vessel wall and even to cross cell membranes. By custom functionalisation of the particles' surfaces, they can selectively bind to a defined biological entity (like cells or degraded extracellular matrix molecules) and deliver drugs or therapeutic DNA for targeted therapy.
By applying a controlled external magnetic field it is possible to perform different actions on the magnetic particles such as applying a mechanic force on the nanoparticles to guide them to a specific location and retaining them there for drug release (magnetic drug targeting, magnetic gene transfection); specifically heating the magnetic nanoparticles (magnetic hyperthermia); changing the local magnetic field in the particle's environment (MRI contrast agents, magnetic cell labelling); generating a specific magnetic signal that can be read from the outside (magnetic nanoparticle imaging); etc. All applications will benefit from a quantitative knowledge of the magnetic nanoparticle distribution to increase suitability, patient safety and efficacy.
A non-invasive quantitative technique for magnetic nanoparticle imaging is at present not established, although several proposals have been made in literature. A first suggestion is Magnetic Particle Imaging (MPI) which is able to image the magnetic particles at very high speed, but is unable to quantitatively determine the concentration of the magnetic nanoparticles. The technique was suggested by Gleich and Weizenecker in Nature 435 (2005) pp 1214-1217. The principle of MPI is based on the nonlinearity of the particles' magnetization curve. When subject to an oscillating magnetic field, the spectrum of the responding magnetization contains not only the base frequency but also higher harmonics that are exploited for imaging.
An alternative is to use magnetorelaxometry measurements as proposed by Flynn and Bryant in Physics in Medicine and Biology 50 (2005) 1273-1293. Magnetic nanoparticles can be activated using an external magnetic field where the single domains of the superparamagnetic nanoparticles are aligned with the local magnetic field. When switching off the external magnetic field, magnetic relaxation occurs following two different relaxation processes (Brown and Néel). The magnetic field originating from the particles in the different positions can be measured using sensitive magnetic field sensors such as superconducting quantum interference devices (SQUIDS).
Electron paramagnetic resonance (EPR) and pulsed EPR detection as described by Teughels and Vaes in International patent application WO2010/037800 developed by Teughels and Vaes is able to sense the concentration of particles. Quantification of the concentration in a single voxel has been reported by Gamarra in International journal of Nanomedicine 5 (2010) pp 203-211. There is still room for an accurate spatial reconstruction of magnetic nanoparticles starting from EPR measurements.